Hepatitis E virus (HEV) infections cause serious morbidity and mortality, especially in pregnant women. Few population-based studies have characterized HEV epidemiology. Proposed is a two-year, multi-component, population-based study to describe the epidemiology and quantify the burden of HEV infections and disease in rural Bangladesh (Matlab District). These studies will be nested within a population of 105,000 under intensive longitudinal health surveillance since 1966. This unique research setting, maintained by the International Center for Diarrheal Disease Research, represents the most accurate and oldest population health surveillance in the developing world. Evidence suggests Bangladesh is HEV endemic, yet no known studies have examined HEV there. The age-specific population prevalence of 1gM and lgG antibodies to HEV will be determined using a random sample of 1030 individuals from the Matlab cohort. A large proportion of the population is under age 15, allowing a description of HEV antibody prevalence among children using improved, reliable assays. Data will be collected at baseline, 12, and 18 months. Incidence of HEV infection and disease will be calculated from HEV seroconversion rates and by extracting reports of hepatitis disease from surveillance system records. A ratio of asymptomatic HEV infections to clinical HEV will be estimated. A nested case-control study is also proposed during the 18-month period to identify potential risk factors associated with sporadic HEV disease. Contaminated water is known to precipitate HEV outbreaks, but risk factors for sporadic HEV are unknown. A visual algorithm will identify potential HEV cases near the time of infection. Only anti-HEV 1gM positive cases will be enrolled. Two HEV-naive controls will be age-matched to a case. A questionnaire will assess potential behavioral, animal and environmental risk factors associated with incident HEy. Multiple logistic regression will be used to model risk factors. Using GIS, cases will be analyzed for spatial or temporal clustering. Virus isolates from acute cases will be sequenced for a phylogenetic analysis of Bangladesh HEy. These studies in a well-defined South-East Asian population will provide a comprehensive epidemiologic profile of endemic and epidemic HEV in a high risk population, and could form the basis for future preventive interventions, such as vaccine trials.